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Combined Phase 2b/3, Double-Blind, Randomized, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Filgotinib in the Induction and Maintenance of Remission in Subjects with Moderately to Severely Active Ulcerative Colitis -

SLCTR Registration Number

SLCTR/2018/025


Date of Registration

15 Aug 2018

The date of last modification

Aug 15, 2018



Application Summary


Scientific Title of Trial

Combined Phase 2b/3, Double-Blind, Randomized, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Filgotinib in the Induction and Maintenance of Remission in Subjects with Moderately to Severely Active Ulcerative Colitis


Public Title of Trial

Filgotinib in the Induction and Maintenance of Remission in Adults With Moderately to Severely Active Ulcerative Colitis


Disease of Health Condition(s) Studied

Ulcerative Colitis


Scientific Acronym

None


Public Acronym

SELECTION1


Brief title

Filgotinib in the Induction and Maintenance of Remission in Adults With Moderately to Severely Active Ulcerative Colitis


Universal Trial Number

None


Any other number(s) assigned to the trial and issuing authority

NCT02914522 (Clinicaltrials.gov), 2016-001392-78 (EUCTR)


Trial Details


What is the research question being addressed?

What is the efficacy and safety of Filgotinib in the induction and maintenance treatment of moderately to severely active Ulcerative Colitis in participants who are biologic-naive and biologic-experienced?


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Double blinded


Control

Placebo


Assignment

Parallel


Purpose

Treatment


Purpose

Phase 2-3


Intervention(s) planned

Study sites: Colombo North Teaching Hospital, Ragama Teaching Hospital Karapitiya, Galle, Kandy Teaching Hospital, Kandy

The study is divided into 2 parts (induction study and maintenance study). Based on protocol eligibility criteria, subjects will be screened for enrolment in either Cohort A (biologic naïve patients) or Cohort B (biologic experienced patients)

Induction study

Subjects who meet protocol eligibility criteria will be assigned to the respective Cohort and subsequently randomized using an interactive system (Interactive Web Response System [IWRS] in a blinded fashion in a 2:2:1 ratio to 1 of 3 treatments as follows;

Treatment 1 (n = 260): filgotinib 200 mg and placebo-to-match (PTM) filgotinib 100 mg, once daily Treatment 2 (n = 260): filgotinib 100 mg and PTM filgotinib 200 mg, once daily Treatment 3 (n = 130): PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily

Study medication will be administered orally, for a total duration of 10 weeks.

Maintenance study

Subjects in Cohort A and B who complete the Induction Study and achieve either MCS (Mayo Clinic Score response) or EBS (establishing endoscopy/bleeding/stool) remission criteria at Week 10 will be re-randomized in a blinded fashion in a 2:1 ratio to either the same dose of filgotinib or placebo into the Maintenance Study at week 11 and will continue in blinded treatment till week 58 (total of 48 weeks). Subjects who complete all procedures per protocol, will have the option to continue study drug in a blinded fashion in the long term extension study.

Subjects who are non-responders based on the results of the Week 10 assessments will be offered the option to receive open-label filgotinib by entering into the LTE study (GS-US-419-3899). Subjects meeting disease worsening criteria after week 11 or later must be discontinued from blinded treatment and will be offered the option to receive open-label filgotinib 200 mg by entering into the LTE study.

Standard management will be offered to the subjects given that subjects on following therapies must be willing to remain on stable doses for the noted times;

a) Oral 5-aminosalicylate (5-ASA) compounds provided the dose prescribed has been stable for at least 4 weeks prior to randomization; dose must be stable for first 10 weeks after randomization

b) Azathioprine, 6-MP or MTX provided the dose prescribed has been stable for 4 weeks prior to randomization; dose must be stable for first 10 weeks after randomization

c) Oral corticosteroid therapy (prednisone prescribed at a stable dose <30 mg/day or budesonide prescribed at a stable dose of <9 mg/day) provided the dose prescribed has been stable for 2 weeks prior to randomization; dose must be stable for first 14 weeks after randomization.

Blinding will be maintained by Interactive Web Responsive System (IWRS), all the blinded Investigational product will be having the similar labels of “Filgotinib & Matching Placebo”

Participants, Healthcare providers and data collectors will be blinded to the intervention status.


Inclusion criteria

  1. Males and non-pregnant, non-lactating females, ages 18 to 75 years, inclusive based on the date of the screening visit

  2. Documented diagnosis of ulcerative colitis of at least 6 months and with a minimum disease extent of 15 cm from the anal verge. Documentation should include endoscopic and histopathologic evidence of UC. (note: a surveillance colonoscopy is required at screening in individuals with a history of ulcerative colitis for 8 or more years, if one was not performed in the prior 24 months.

  3. Moderately to severely active ulcerative colitis Severity index will be evaluated using a centrally read endoscopy score > 2, arectal bleeding score > 1, a stool frequency score > 1 and PGA (physician global assessment) of > 2 as determined by the Mayo clinic scoring system with endoscopy occurring within 14 days to first dose of study drug; total score must be between 6 and 12, inclusive.

  4. Previously demonstrated an inadequate clinical response, loss of response to, or intolerance to at least 1 of the following agents: corticosteroids, immunomodulators, tumor necrosis factor alpha (TNFa) antagonists, or vedolizumab


Exclusion criteria

  1. Presence of Crohn's disease, indeterminate colitis, ischemic colitis, fulminant colitis, ulcerative proctitis, or toxic mega-colon 2.Active tuberculosis (TB) or history of latent TB that has not been treated
  2. Use of any concomitant prohibited medications as described in the protocol (details are available at the SLCTR)


Primary outcome(s)

Induction study:

  1. Proportion of Participants Achieving Remission Based on Components of Mayo Clinic Score (MCS) at Week 10 [ Time Frame: Week 10 ]

Maintenance study :

  1. Proportion of Participants Achieving Remission Based on Components of MCS at Week 58 [ Time Frame: Week 58 ]

Primary outcome(s) - Time of assessment(s)

Induction study:

  1. Proportion of Participants Achieving Remission Based on Components of Mayo Clinic Score (MCS) at Week 10 [ Time Frame: Week 10 ]

Maintenance study

  1. Proportion of Participants Achieving Remission Based on Components of MCS at Week 58 [ Time Frame: Week 58 ]

Secondary outcome

Induction study:

  1. Proportion of Participants Achieving MCS Remission at Week 10 [ Time Frame: Week 10 ]
  2. Proportion of Participants Achieving Endoscopic Subscore of 0 at Week 10 [ Time Frame: Week 10 ]
  3. Proportion of Participants Achieving Histologic Remission at Week 10 [ Time Frame: Week 10 ]
  4. Proportion of participants achieving MCS remission (alternative definition) at Week 10 [ Time Frame: Week 10 ]
  5. Pharmacokinetic Plasma Concentrations of Filgotinib and its Metabolite GS-829845 [ Time Frame: Week 4 postdose and Week 10 predose ]

Maintenance study:

  1. Proportion of Participants Achieving MCS Remission at Week 58 [ Time Frame: Week 58 ]
  2. Proportion of Participants Achieving Remission Based on Components of MCS at Weeks 10 and 58 [ Time Frame: Weeks 10 and 58 ]
  3. Proportion of Participants Achieving 6-Month Corticosteroid-Free Remission Based on Components of MCS at Week 58 [ Time Frame: Week 58 ]
  4. Proportion of Participants Achieving Endoscopic Subscore of 0 at Week 58 [ Time Frame: Weeks 58 ]
  5. Proportion of Participants Achieving Histologic Remission at Week 58 [ Time Frame: Week 58 ]
  6. Proportion of participants achieving MCS remission (alternative definition) at Week 58 [ Time Frame: Week 58 ]
  7. Pharmacokinetic Plasma Concentrations of Filgotinib and its Metabolite GS-829845 [ Time Frame: Week 26 (predose or postdose) and Week 58 predose ]

Secondary outcome(s) - Time of assessment(s)

Induction study:

  1. Proportion of Participants Achieving MCS Remission at Week 10 [ Time Frame: Week 10 ]
  2. Proportion of Participants Achieving Endoscopic Subscore of 0 at Week 10 [ Time Frame: Week 10 ]
  3. Proportion of Participants Achieving Histologic Remission at Week 10 [ Time Frame: Week 10 ]
  4. Proportion of participants achieving MCS remission (alternative definition) at Week 10 [ Time Frame: Week 10 ]
  5. Pharmacokinetic Plasma Concentrations of Filgotinib and its Metabolite GS-829845 [ Time Frame: Week 4 postdose and Week 10 predose ]

Maintenance study:

  1. Proportion of Participants Achieving MCS Remission at Week 58 [ Time Frame: Week 58 ]
  2. Proportion of Participants Achieving Remission Based on Components of MCS at Weeks 10 and 58 [ Time Frame: Weeks 10 and 58 ]
  3. Proportion of Participants Achieving 6-Month Corticosteroid-Free Remission Based on Components of MCS at Week 58 [ Time Frame: Week 58 ]
  4. Proportion of Participants Achieving Endoscopic Subscore of 0 at Week 58 [ Time Frame: Weeks 58 ]
  5. Proportion of Participants Achieving Histologic Remission at Week 58 [ Time Frame: Week 58 ]
  6. Proportion of participants achieving MCS remission (alternative definition) at Week 58 [ Time Frame: Week 58]
  7. Pharmacokinetic Plasma Concentrations of Filgotinib and its Metabolite GS-829845 [ Time Frame: Week 26 (predose or postdose) and Week 58 predose ]


Target number/sample size

70 from Sri Lanka (Arm 1=28; Arm 2=28; Arm 3=14)


Countries of recruitment

Malaysia, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sri Lanka, Sweden, Taiwan, Province of China, Ukraine, United Kingdom, United States


Anticipated start date

2018-08-15


Anticipated end date

2019-12-31


Recruitment status

Pending


State of ethics review approval

Approved by Ethics Review Committee, Faculty of Medicine, University of Kelaniya on 13 March 2018


Funding source

Gilead Sciences, Inc. 333 Lakeside Drive Foster City, CA 94404, USA



Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Prof Arjuna de Silva
Consultant Physician
Room No. 2, Ward No. 22, Professorial medical unit, Colombo North Teaching Hospital, Ragama-11010, Sri Lanka

+ 94-777572379

apdesilva@kln.ac.lk

Contact Person for Public Queries

Prof Arjuna de Silva
Consultant Physician
Room No. 2, Ward No. 22, Professorial medical unit, Colombo North Teaching Hospital, Ragama-11010, Sri Lanka

+ 94-777572379

apdesilva@kln.ac.lk


Primary study sponsor/organization

Gilead Sciences, Inc
Gilead Clinical Study Information Center
333 Lakeside Drive Foster City, CA 94404, USA
Tel: +1-833-445-3230

GileadClinicalTrials@gilead.com

Secondary study sponsor (If any)

None